Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure-bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial

Clin Res Cardiol. 2020 Apr;109(4):417-425. doi: 10.1007/s00392-019-01521-y. Epub 2019 Jun 29.


Background: Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance.

Methods: In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients' care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h.

Results: 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function.

Conclusion: Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion.

Drain trial: ClinicalTrials.gov number NCT03592836.

Keywords: Advanced heart failure; Bolus intermittent; Continuous infusion; Diuretic resistance; Furosemide.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Central Venous Pressure / drug effects
  • Chronic Disease
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance
  • Edema / diagnosis
  • Edema / physiopathology
  • Edema / prevention & control*
  • Female
  • Furosemide / administration & dosage*
  • Furosemide / adverse effects
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Italy
  • Male
  • Middle Aged
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage*
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Time Factors
  • Treatment Outcome


  • Sodium Potassium Chloride Symporter Inhibitors
  • Furosemide

Associated data

  • ClinicalTrials.gov/NCT03592836